tbuckley/cabot-search huggingface dataset:
P09.08.B UNDERSTANDING THE HOLISTIC NEEDS OF PEOPLE LIVING WITH GLIOMA AND THEIR CAREGIVERS: A THEMATIC ANALYSIS OF THE SEMI-STRUCTURED INTERVIEWS FOR THE COBRA STUDY
Authors: E Baddeley, S Sivell, A Retzer, A Nelson, H Bulbeck, K Seddon, R Grant, R Adams, C Watts, O Aiyegbusi, P Kearns, S Rivera, L Dirven, M Calvert, A Byrne
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The needs of people with brain tumours are unique, particularly in terms of neurocognitive impacts, and their subsequent effects on primary caregivers. Evidence suggests that those with brain tumours and their primary caregivers experience unmet needs in the clinical care setting. MATERIAL AND METHODS Semi-structured interviews with people with glioma and their caregivers, in the UK, with the aim to understand their priorities and lived experience of glioma, its treatment and treatment aims. Interviews formed part of a study to identify a core outcome set (COS) for glioma interventional trials (COBra study). The interview data were further analysed to identify concepts of importance to people with glioma and their caregivers within the clinical care setting. RESULTS Nineteen people with glioma and seven caregivers were interviewed (n=6 glioblastoma, n=4 astrocytoma, n=4 anaplastic astrocytoma/ oligodendroglioma, n=2 oligodendroglioma n=1 PXA tumour, n=1 ‘oligodendroglioma grade 3’ and n=1 ‘glioma grade 3’). Themes identified related to unmet needs and frustrations around communication, access to/need for support, caregiver impacts, neurocognitive symptoms and impacts to activities of daily living. Our findings also indicate the impact of treatment side effects, and how patients and caregivers negotiated tolerability in terms of trade-offs across the spectrum of glioma. Additionally, it was perceived that glioma grade did not correlate with symptom burden, and for those with longer survival, issues relating to late side effects were prominent - highlighting significant unmet needs across the spectrum of disease. Most described the lack of support and being left to deal with many of the unique burdens of the disease alone. Caregivers needs corresponded to the particular challenges experienced by their loved one, including late and longer-term effects of the disease, particularly neurocognitive impacts and the subsequent effects to patients’ activities of daily living as a result. Psychosocial impacts on caregivers were prevalent, reported by caregivers and also reported by patients interviewed with no caregiver present. CONCLUSION The qualitative data highlights the unmet needs of people with glioma and their caregivers, which are complex, unique and affect all those across the spectrum of glioma. As such, there is a need for a consistent and appropriate assessment of needs for patients and their caregivers in clinical practice, which need to incorporate the key concepts, such as communication, tolerability and support. These findings support further investigation into a holistic needs assessment for those with glioma.
P13.09.B FULLY AUTOMATED BRAIN METASTASES SEGMENTATION USING T1-WEIGHTED CONTRAST-ENHANCED MR IMAGES BEFORE AND AFTER STEREOTACTIC RADIOSURGERY
Authors: H Kanakarajan, W De Baene, E Verhaak, P Hanssens, M Sitskoorn
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Brain metastases (BM) represent the most common intracranial tumor in adults. An estimated 20% of all patients with cancer will develop BM. Stereotactic Radiosurgery (SRS) is a major treatment option for BM. For SRS treatment planning and outcome evaluation, magnetic resonance images (MRI) are acquired before and at multiple stages during the follow-up. Accurate segmentation of brain tumors on MRI is crucial for treatment planning and response evaluation. Detection and segmentation of BM which is a tedious and time-consuming task for many radiologists could be optimized with machine learning METHODS . The accuracy of the auto-segmentation, however, is influenced by the presence of false-positive and false-negative segmentation. There are studies which evaluated the segmentation performance of several deep learning algorithms, these were mainly focused on training and testing the models on either the pre-treatment or post-treatment images. The purpose of this study was to investigate a well-known deep learning approach (nnU-Net) for BM segmentation and to evaluate its performance on both pre-treatment and post-treatment images to assess if it could be a handy tool for the clinicians. METHODS Pre-treatment T1-weighted brain MRIs which were contrast-enhanced with triple-dose gadolinium were collected retrospectively for 266 patients with BM. Scans were made as part of clinical care at the Gamma Knife Center of the Elisabeth-TweeSteden Hospital (Tilburg, the Netherlands). All patients underwent Gamma Knife Radiosurgery, a form of SRS. This total of 266 patients were randomly split into 210 patients for model training/validation and 56 patients for testing. For these 56 patients used for testing, the post treatment follow-up T1-weighted brain MRI scans which were contrast-enhanced with single-dose gadolinium were also retrospectively collected. The nnU-Net model was trained with the pre-treatment training data, and then tested separately against the pre-treatment and follow-up data. RESULTS The model obtained a Dice score of 0.91 when tested with the pre-treatment images and a Dice score of 0.80 when tested with the follow-up after treatment T3 images. The False Negative Rate (FNR) when tested with the pre-treatment images was 0.07 and 0.24 when tested with post-treatment T3 images. CONCLUSION The model achieved a good performance score for pre-treatment images. The nnU-Net model can automatically detect and segment brain metastases with high sensitivity, and low FNR for treatment planning. This could be a beneficial tool for clinicians and assist SRS management for diagnosis and treatment planning. Though there is a decline in the Dice score and an increase in the FNR of the model for the post-treatment images, the performance still remained higher than in other similar studies.
P11.44.A THE ROLE OF RADIOTHERAPY IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A MULTICENTER COHORT STUDY
Authors: C Y M N Jansma, J H Coert, D J Grünhagen, C Verhoef, E Martin, W Taal
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS), of which 40% are associated with neurofibromatosis type 1 (NF1). Current treatment in localized disease mainly revolves around surgical excision, yet MPNSTs harbor a high probability of local recurrence (LR). Radiotherapy (RT) is increasingly being used, as it improves local control in STS, yet does not impact survival. Nevertheless, its use is controversial in some cases as major wound complications can be much higher and NF1 patients harbor a potential higher risk for secondary malignancies as MPNST commonly arise within plexiform neurofibromas. This study evaluates the use of RT in these rare tumors and tries to understand its impact in local control, especially in the NF1 setting. MATERIAL AND METHODS Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Demographic and treatment differences, especially the use of RT, between NF1 and non-NF1 were analyzed. Univariate and multivariable logistic regression analyses were used to identify factors independently associated with the use of radiotherapy. Multivariate Cox regression analyses were performed to identify factors associated with LR in NF1 patients. RESULTS A total of 528 patients (31.8% NF1) were included, of which 149 (28.2%) developed a LR. RT was administered in 53.2% of patients (55.6% in NF1). Of these, 26.7% received neoadjuvant RT, and 71.2% adjuvant RT. The use of both treatment modalities was similar between patients with and without NF1. Multivariable regression showed that microscopically positive margins and high-grade tumors were independent factors for the use of RT. The rate of RT use in NF1 did not alter after correcting for tumor-, patient- and surgical factors. RT did not impact overall survival in sporadic and NF1 associated MPNST. In NF1 patients, microscopically positive margins (R1) (HR 3.2; 95% CI, 1.41-7.62), tumor size &amp;gt;5cm (HR 2.2; 95% CI, 1.14-4.3), and a high grade (HR 3.13; 95% CI, 1.23-7.98) were independent risk factors for the development of a LR. Correcting for tumor-, patient- and surgical factors, use of RT was not associated lower rates of LR, in contrast to the sporadic population. CONCLUSION Radiotherapy is commonly used in MPNST treatment regardless of its origin in NF1. While it may impact LR rate in sporadic patients, this is less clear in NF1 patients. Further studies are needed to evaluate its role and indications in NF1 associated MPNST.
P11.68.A INTRA-ARTERIAL ADMINISTRATION OF [68GA]GA-PSMA-11 IN MALIGNANT PRIMARY AND SECONDARY BRAIN TUMOURS; A NOVEL APPROACH THAT SIGNIFICANTLY INCREASES TUMOUR UPTAKE AND POTENTIAL OF/FOR THERANOSTIC STRATEGIES
Authors: I J Pruis, P van Doormaal, R K Balvers, M J van den Bent, A A Harteveld, L C de Jong, M Konijnenberg, M Segbers, V van Dis, T P van den Bosch, F A Verburg, M Smits, S E M Veldhuijzen van Zanten
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Primary and secondary brain tumours carry a dismal prognosis and require new treatment strategies. First studies into novel radionuclide therapies have thus far yielded little success, potentially because of limitary uptake in tumour upon intravenous (IV) administration. The aim of the present study was to show that intra-arterial (IA) administration of radiopharmaceuticals will lead to much higher uptake and, consequently, to higher delivered dose to the tumour, which convincingly outweighs the systemic non-target uptake. MATERIAL AND METHODS Ten patients with malignant brain tumours (n=5 high-grade glioma (HGG), n=5 brain metastasis (BM)) twice received 1.5 MBq/kg [68Ga]Ga-PSMA-11 followed by PET-MRI at 90, 165 and 240 minutes post-administration, first upon IV and subsequently upon selective IA administration, with a median interval time of 5 days. Standardised uptake values (SUVs) were calculated for tumour, and non-target sites (contralateral healthy brain, salivary glands and liver) using volumes of interest (VOIs). Tumour-to-liver (T/L), tumour-to-salivary gland (T/SG) uptake-ratios and simulated achievable tumour doses with either [177Lu]Lu- or [225Ac]Ac-PSMA were calculated for each patient. Paired T-test and Wilcoxon signed rank-test were performed to compare outcomes. RESULTS All patients showed significantly higher uptake in tumour following IA administration compared to IV administration, with a median SUVmax of 142.8 (range: 31.3-336.8) versus 10.5 (range: 5.1-17.1, P=0.005). Healthy brain showed no significant uptake, independent of the route of administration (SUVmean range: &amp;lt;0.1-0.1). Uptake at non-target sites was comparable following IA and IV administration, resulting in more favourable T/SG-ratios of 8.4 (median, range: 1.8-18.9) for IA versus 1.8 (0.9-7.0) for IV; P=0.005 and T/L-ratios of 26.5 (7.4-68.7) for IA versus 1.8 (0.9-7.0) for IV; P=0.005. Simulations showed a maximum delivered dose to the tumours for a single treatment cycle to be 68 Gy (median, range: 5-282) for [177Lu]Lu- and 78 Gy (5-174) for [225Ac]Ac-PSMA when administered intra-arterially, versus 10 Gy (1-37) and 18 Gy (1-49), when administered intra-venously. CONCLUSION Selective IA administration of radiopharmaceuticals in malignant brain tumours leads to a significant and therapeutically relevant increase in target to non-target uptake ratios. This observation opens new avenues for the development of theranostic strategies for patients with HGG and BM whom we, to date, have no curative treatment to offer.
P09.02.B THE RELATIONSHIP BETWEEN SYMPTOMS AND THE SOCIAL DETERMINANTS OF HEALTH AMONG THE PRIMARY BRAIN TUMOR POPULATION: A SYSTEMATIC REVIEW
Authors: M L Stockdill, M Johnson, Z Karim, D Cooper, T S Armstrong, A L King
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Social determinants of health (SDoH) account for up to half of all health outcomes in the general population, but their impact on symptoms is less understood, especially in rare cancers such as primary brain tumors (PBT). MATERIAL AND METHODS We reviewed the literature and examined the relationship between SDoH and mood and neurocognitive symptoms in the PBT population. PubMed, EMBASE, and CINAHL identified 3,006 publications. SDoH were defined using PROGRESS criteria (Place of residence, Race/ethnicity, Occupation, Gender, Religion, Education, Socioeconomic status, Social capital). Two individuals screened and assessed study bias. RESULTS Of 3,006 abstracts identified, 150 full text articles were assessed for eligibility and 48 studies were included with a total sample of 28,454 PBT participants. 27 studies were cross-sectional with the majority from single institutions in the US (12), Germany (10), or Netherlands (5). Sample sizes varied from 27 to 15,320. 22 studies examined the relationship with 1 of the PROGRESS categories and no study examined all 8. 4 studies measured place of residence, 2 race/ethnicity, 13 occupation, 43 gender, 1 religion, 18 education, 4 socioeconomic status, and 15 social capital. 37 studies reported on mood related symptoms with 20 focused on depression, 14 anxiety, and 11 distress. 15 studies assessed neurocognitive symptoms, while 4 assessed both mood and neurocognition. Among studies assessing neurocognition, 1 found a relationship with place of residence and socioeconomic status, 7 out of 10 reported a relationship with education, and 7 of 11 found no relationship with gender. None examined race/ethnicity or religion. Disparate results were found related to occupation. Among the 37 studies assessing mood, results were disparate except for place of residence, which related rural residence to depressive symptoms. Bias assessment revealed that 61% of the studies were fair in quality, 31% poor, and 8% good indicating the majority of studies had evidence of bias. CONCLUSION Most studies were descriptive or exploratory and lacked comprehensive inclusion of SDoH, which limited the opportunity to perform meta-analysis. This is the first systematic review examining the relationship of symptoms in the PBT population and SDoH to date. Future studies should use standardized collection of SDoH, reduce study bias, and encourage inclusion of diverse samples to identify gaps for the development of future interventions.
P10.15.A THE ROLE OF NONCODING RNAS IN THE PROGRESSION OF IDH-MUTANT ASTROCYTOMAS TO GRADE 4
Authors: A Hartewig, S Jaatinen, M Annala, P Helén, J Haapasalo, W Zhang, H Haapasalo, M Nykter, K J Rautajoki
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Low grade IDHmutant astrocytomas are heterogeneous brain tumors that have a prognosis of 7-10 years. However, this prognosis is significantly worsened if the tumors progress to grade 4 astrocytomas. Noncoding RNAs, especially long noncoding RNAs and microRNAs, have been studied increasingly in the past years in various cancers including gliomas, and a general dysregulation was observed. The dysregulated RNAs were shown to regulate crucial disease processes, such as cell proliferation, apoptosis, and therapy resistance. Thus, several noncoding RNAs were identified as promising biomarkers and potential therapy targets, some of which are already being tested in clinical trials. Despite advances in the field, little is known about the role of noncoding RNAs in the progression of IDHmutant astrocytomas. MATERIAL AND METHODS We collected matched samples and clinical information from six IDHmutant astrocytoma patients before and after progression to grade 4 and subjected them to RNA- and small RNA-sequencing. We defined which microRNAs and long noncoding RNAs were significantly up- or downregulated upon progression. We also predicted the target genes of differentially expressed microRNAs utilizing machine learning algorithms and experimentally validated databases. The predicted targets were filtered for negative correlation in gene expression, and their biological relevance was assessed with gene set analysis and literature research. RESULTS We found 33 differentially expressed microRNAs upon progression, out of which 19 were up- and 14 were downregulated. A total of 443 negatively correlating targets were identified for the microRNAs (0-115 per microRNA). The target genes were associated with DNA repair, proliferation, and G-Protein coupled receptor signaling. Furthermore, we observed 19 up- and 14 downregulated lncRNAs within the differentially expressed genes. Six of them have been reported to be cancer-related, including known tumor-suppressors and lncRNAs known to promote cell proliferation, invasion and migration. CONCLUSION The study identified a number of noncoding RNAs associated with the progression of IDHmutant astrocytoma to grade 4. Further studies are needed to evaluate their potential to act as biomarkers or therapy targets.
OS12.7.A IMPLEMENTATION OF A NATIONAL AYA MOLECULAR TUMOR BOARD: REPORT FROM THE CANADIAN AYA NEURO-ONCOLOGY NETWORK
Authors: M Lim-Fat, J Bennett, R Al-Bati, S Climans, A Chan, N Massey, D S Tsang, C Hawkins, U Tabori, S Das
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The adolescent and young adult (AYA) population (15-39 years) is a unique and understudied population within neuro-oncology, and their care requires expertise across pediatric and adult-type brain tumors. Current challenges in AYA neuro-oncology include fragmented care across pediatric and adult hospitals, low inclusion in clinical trials, unique survivorship considerations and a lack of standard-of-care therapies for this population. MATERIAL AND METHODS We report on a two-year national effort from the Canadian AYA Neuro-Oncology Network (CANON) to implement national AYA rounds. The aims of the rounds are to discuss challenging cases, encourage and review the utility standardized molecular testing, and provide point-of-care multidisciplinary recommendations benefiting from the expertise of pediatric and adult providers across several tertiary and community centers. RESULTS Since April 2021, the Canadian national AYA rounds have occurred biweekly on a virtual secure platform. Over 2 years, 138 cases have been discussed; 23% of patients were 15-20 years old, 33% were 21-30 years old and 26% were 31-40 years old. Cases discussed included low grade gliomas (39%), followed by high grade gliomas (33%), ependymomas (6.5%), medulloblastomas (6.5%) and others (9.4%). A total of 240 participants across 25 institutions across Canada have attended the rounds, spanning adult and pediatric neurosurgery, neuro-pathology, neuro-oncology, radiation oncology and radiology. A prospective database of cases presented at our AYA rounds, matching molecular characterization, choice of therapies and relevant clinical outcomes has been initiated and interim data will be presented at the meeting. CONCLUSION Virtual national AYA-neuro-oncology multi-disciplinary rounds have raised awareness of current gaps and possible nation-wide solutions to improve the care of AYA brain tumors. Leveraging this network, our group has published guidelines for molecular testing in AYA brain tumors and is employing this platform for ongoing research and clinical collaborations.
P11.21.A LONG-TERM SURVIVAL WITH IDH WILDTYPE GLIOBLASTOMA: FIRST RESULTS FROM THE ETERNITY BRAIN TUMOR FUNDERS’ COLLABORATIVE CONSORTIUM (EORTC 1419)
Authors: M Weller, J Felsberg, D Gramatzki, E Le Rhun, J Clarke, R Soffietti, W Wick, O Chinot, F Ducray, P Roth, K McDonald, P Hau, A F Hottinger, J Reijneveld, O Schnell, C Marosi, M Glantz, A Darlix, G Lombardi, D Krex, M Glas, D A Reardon, M J van den Bent, F Lefranc, U Herrlinger, E Razis, A F Carpentier, S Phillips, R Rudà, A Wick, E Tabouret, D Meyronet, C Maurage, E Rushing, R Rapkins
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. METHODS European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and by the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumors, prognostic factors were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. RESULTS At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterized) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% CI 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p&amp;lt;0.001) and had a high rate (48.8%) of MGMT promoter unmethylated tumors. CONCLUSION s Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.
P15.11.B POSTOPERATIVE68GA-DOTATATE/PET-CT IMAGING IS PROGNOSTIC FOR PROGRESSION-FREE SURVIVAL IN MENINGIOMA WHO GRADE 1: A PROSPECTIVE SINGLE-CENTER STUDY
Authors: N Teske, A Biczok, S Quach, F J Dekorsy, R Forbrig, R Bodensohn, M Niyazi, J Tonn, N L Albert, C Schichor, M Ueberschaer
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Microsurgical tumor resection represents the first-line treatment for symptomatic meningiomas, and extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. However, prognostic relevance of postoperative PET for progression-free survival in meningiomas remains unclear. METHODS We conducted a prospective study including patients with surgically removed meningioma WHO grade 1 and collected clinical and imaging data. All patients received postoperative MRI and 68Gallium-DOTATATE/PET, and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS We included 46 patients with 49 tumors. Mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029) whereas MRI was not. 20/20 patients (100%) with negative PET findings remained recurrence-free. Location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION Our data show that 68Ga-DOTATATE/PET is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.